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Predicting High-Dose-Rate Brachytherapy Boost Benefit Using Hypoxia and Angiogenesis Gene Expression in Localised

T Lodhi1, M Reardon2, C G Quiles2

  • 1Division of Cancer Sciences, University of Manchester, UK; Department of Clinical Oncology, The Christie Hospital NHS Trust, Manchester, UK.

Clinical Oncology (Royal College of Radiologists (Great Britain))
|April 17, 2026
PubMed
Summary
This summary is machine-generated.

Gene expression profiles can predict which prostate cancer patients benefit from high-dose-rate brachytherapy boost (HDR-BTb). Low SLC2A1 and high CD34 expression, along with their interaction, indicate benefit from HDR-BTb, aiding patient selection for improved outcomes.

Keywords:
BiomarkerBrachytherapyGene expressionHypoxiaProstate cancerRadiotherapy

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Area of Science:

  • Oncology
  • Genomics
  • Radiotherapy

Background:

  • High-dose-rate brachytherapy boost (HDR-BTb) combined with external beam radiotherapy (EBRT) improves outcomes for localized prostate cancer (PCa).
  • Despite dose escalation, approximately 21% of patients experience relapse.
  • Genomic validation of hypoxia and angiogenesis biomarkers at the transcriptomic level is needed to refine patient selection for HDR-BTb.

Purpose of the Study:

  • To investigate if hypoxia- and angiogenesis-related gene expression profiles can predict clinical benefit from HDR-BTb escalation in localized prostate cancer.
  • To refine patient selection for dose escalation in prostate cancer treatment.

Main Methods:

  • Whole transcriptome analysis using Clariom S microarrays in a phase III trial comparing EBRT alone versus EBRT+HDR-BTb.
  • Evaluation of gene expression for CD34, SLC2A1, HIF1A, SPP1, and established hypoxia signatures.
  • Statistical analysis using log-rank tests and Cox proportional hazards models to assess prognostic and predictive value.

Main Results:

  • High HIF1A and CD34 expression were prognostic for worse metastasis-free survival (MFS) and biochemical relapse-free survival (bRFS), respectively.
  • Predictive analysis indicated HDR-BTb benefit in patients with low HIF1A, low SLC2A1, low 32-gene hypoxia scores, and high CD34 expression.
  • A significant interaction between SLC2A1 and CD34 expression predicted HDR-BTb benefit (P = .017).

Conclusions:

  • Gene expression has limited prognostic value, but specific profiles predict benefit from HDR-BTb.
  • Low SLC2A1 and high CD34 expression, along with their interaction, are key predictors of HDR-BTb benefit.
  • Biomarker-led stratification using hypoxia-related gene signatures can improve patient selection for HDR-BTb in prostate cancer.